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Amyloid-β and Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is the second commonest neurodegenerative disorder in the world with a rising prevalence. The pathophysiology is multifactorial but aggregation of misfolded α-synuclein is considered to be a key underpinning mechanism. Amyloid-β (Aβ) and tau deposition are also comorbid associations and especially Aβ deposition is associated with cognitive decline in PD. Some existing evidence suggests that low cerebrospinal fluid (CSF) Aβ42 is predictive of future cognitive impairment in PD. Recent studies also show that CSF Aβ is associated with the postural instability and gait difficulties (PIGD) or the newly proposed cholinergic subtype of PD, a possible risk factor for cognitive decline in PD. The glial-lymphatic system, responsible for convective solute clearance driven by active fluid transport through aquaporin-4 water channels, may be implicated in brain amyloid deposition. A better understanding of the role of this system and more specifically the role of Aβ in PD symptomatology, could introduce new treatment and repurposing drug-based strategies. For instance, apomorphine infusion has been shown to promote the degradation of Aβ in rodent models. This is further supported in a post-mortem study in PD patients although clinical implications are unclear. In this review, we address the clinical implication of cerebral Aβ deposition in PD and elaborate on its metabolism, its role in cognition and motor function/gait, and finally assess the potential effect of apomorphine on Aβ deposition in PD.

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Authors and Affiliations

  1. Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience at King’s College London, De Crespigny Park, London, SE5 8AF, UK

    Dag Aarsland, Dominic Ffytche, Daniel J. van Wamelen, Yi-Min Wan & Kallol Ray Chaudhuri

  2. Parkinson Foundation International Centre of Excellence at King’s College Hospital, Denmark Hill, London, SE5 9RS, UK

    Ee Wei Lim, Raquel Natalia Taddei, Daniel J. van Wamelen, Yi-Min Wan & Kallol Ray Chaudhuri

  3. Department of Neurology, National Neuroscience Institute (Singapore General Hospital Campus), 20 College Road, Singapore, 169856, Singapore

    Ee Wei Lim & Eng King Tan

  4. Duke-National University of Singapore Graduate Medical School, Singapore, 169857, Singapore

    Ee Wei Lim & Eng King Tan

  5. Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, Reinier Postlaan 4, Postbus 9101, 6500HB, Nijmegen, The Netherlands

    Daniel J. van Wamelen

  6. Department of Psychiatry, Ng Teng Fong General Hospital, 1 Jurong East Street 21, Singapore, 609606, Singapore

    Yi-Min Wan

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Lim, E.W., Aarsland, D., Ffytche, D. et al. Amyloid-β and Parkinson’s disease. J Neurol 266, 2605–2619 (2019). https://doi.org/10.1007/s00415-018-9100-8

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